Restriction of dietary fat, in particular saturated fat, has been promoted since the mid 20th century in order mainly to prevent atherosclerotic disease and overweight, which became increasingly common during the first half of the century [1]. The benefits of dietary fiber were proclaimed around 1970 although proponents of ’coarse food’ have been heard long before. The idea largely emerged from belief systems concerning disturbed bowel function, bloating and ”autointoxication” in the 19th and early 20th century [2]. The popularity of the hypothesis increased dramatically around 1970 when Hugh Trowell, an internist, and Denis Burkitt, a surgeon, launched the idea that dietary fiber would prevent certain age-related, degenerative diseases [3, 4]. For more than 20 years, working at clinics in Kenya and Uganda, both men noted that Western diseases were largely non-existent among the native population. Burkitt, above all, had the greatest success positing the fiber hypothesis. He was a good speaker and also the first to characterize the type of lymphoma that later carried his name, which gave extra weight to his credibility.

The notion that fat is unhealthy has essentially been based on epidemiological studies, in particular the Seven Countries Study [5]. In this study, 12,095 men aged 40-59 were followed for 10 years starting around 1960. The incidence of ischemic heart disease was positively associated with total and saturated fat intakes, which, respectively, explained 25% and 70% of the disease rates among the study populations.

However, despite widespread consensus among nutrition experts today, there is no solid evidence of fat enrichment or fiber depletion being important causes of Western disease. In the Seven Countries Study, US men had more than 100-fold higher incidence of ischemic heart disease than Cretan men despite identical fat intake, 40 percent of dietary energy (E%) [5]. In one large randomized controlled study of nearly 49,000 US women, the Women’s Health Initiative Dietary Modification Trial, no beneficial effect was seen on cardiovascular disease, cancer or total mortality during 8 years’ follow-up by a low-fat, high fiber diet [6]. For the 3.4% of women with diagnosed cardiovascular disease at the start of the trial, a statistically significant increased risk of worsening of cardiovascular disease was seen in the intervention group (relative risk 1.26; 95% confidence interval 1.03-1.54). Diet changes at 6 years after study start (evaluated from food frequency questionnaires), in the intervention group as compared with the control group, were as follows: fruit/vegetables +30%, grains +11%, fiber +16%, total fat –8%, trans fat –22%, saturated fat –23%, monounsaturated fat –23%, carbohydrate +18%. The intervention and control groups differed with regard to intensity of dietary education but not with regard to type of dietary advice.

In contrast to these disappointing findings, in two other studies, subjects with impaired glucose tolerance had a lower risk of being diagnosed with diabetes during 3 years after advice to eat a low-fat, high-fiber diet and to increase their physical activity [7, 8]. The study design precludes any opinion about the independent roles of diet and exercise. In a meta-analysis of randomized controlled trials in humans, restriction of total and saturated fat apparently had no positive overall effect on total mortality or cardiovascular disease [9]. However, in trials with at least 2 years’ follow-up, a 24% reduction of premature death or cardiovascular events was seen (relative risk 0.76; 95% confidence interval 0.65-0.90), although no effect on total mortality was found. In published studies of changing fat intake in the treatment of overweight or obesity, fat restriction seems equally effective as calorie restriction for long-term weight loss [10]. Studies in animals have shown high-fat diets to be a partial cause of both atherosclerosis [11] and insulin resistance [12, 13]. In some of these studies, a rather moderate increase in dietary fat has caused abdominal obesity and insulin resistance, one of the main culprits in Western disease [13]. In other animal experiments, a high-fat diet has led to intracellular fat accumulation, which is suspected of leading to long-term loss of cell function by way of lipotoxicity [14, 15]. This disturbance is closely related to insulin resistance and the metabolic syndrome [16].

With regard to dietary fiber, the evidence from intervention studies is even less convincing. The only published randomized controlled study of increased fiber intake, mainly from whole-grains, resulted in non-significantly (p=0.10) increased risk of death from heart disease among patients with established atherosclerotic heart disease at study start [17]. In several prospective epidemiological studies people who prefer whole-grain cereals to more refined ones have a lower risk of cardiovascular disease [18], but this may possibly represent confounding by other lifestyle factors, rather than a direct effect of dietary fiber. Somewhat surprisingly, the long held notion that colon cancer is prevented by dietary fiber is not supported by available evidence [19-21].

In summary, these and other studies suggest that low-fat diets are slightly better than the average Western diet, while there is less convincing evidence in support of a high fiber intake.

Fruits and vegetables

For people on a Western diet, fruits and vegetables may provide an important source of essential vitamins, minerals and trace elements. However, once nutrient requirements are met it is uncertain whether these foods are important for long-term health in the prevention of Western disease. The high water content of fruits and vegetables is expected to prevent obesity by way of satiation [22]. Several studies found beneficial effects on health-related variables of lifestyle or dietary advice which included increased amounts of fruits and vegetables [23]. In the successful Lyon Diet Heart Trial, fruits and vegetables were some of the foods recommended to the intervention group, which conceivably explained some of the reduced mortality in that group [24]. Epidemiological prospective studies suggest a slightly reduced risk of cardiovascular disease and several types of cancer.

However, no randomized controlled trial has specifically addressed the independent effects of fruit and/or vegetables on the incidence of death or serious disease such as cardiovascular disease or cancer. In a study on males with angina pectoris, Burr and coworkers found no effect on total mortality or cardiovascular disease of advice to eat 4-5 portions of fruit and vegetables and drink at least one glass of natural orange juice daily, and also increase the intake of oats [25]. Hence, there is as yet no strong evidence that a low intake of fruits or vegetables is an independent cause of Western disease.

Calorie restriction

In animal experiments, restriction of dietary energy has been found to increase lifespan in dogs, rats, mice, fish, worms, yeast and fruit flies, but not (yet) in primates [26, 27]. In studies on non-human primates, calorie restriction has not been shown to retard atherosclerosis or prolong life, but markedly beneficial effects have been noted on cardiovascular risk factors [28, 29]. A study on Rhesus monkeys (8 calorie-restricted and 109 controls) starting in 1977 found a relative risk of death of 0.42 (95% CI 0.1-1.4) during the first 25 years in the calorie restricted group. Although the difference is far from statistically significant, it is conceivable that a larger trial or longer duration would be able to show a beneficial effect.

An observational study in 18 middle-aged calorie-restricted humans suggest that the atherosclerotic process can be attenuated [30]. At age 50 years, after an average of 6 years of calorie restriction, the thickness of the intima-media part of the carotid artery (the large neck artery) was 0.5 ±0.1 mm compared to 0.8 ±0.1 mm in 18 comparison subjects. Cardiovascular risk factor levels were excellent, including C-reactive protein at 0.3 ±0.2 µg/mL in the calorie restricted group compared to 1.6 ±2.2 in the comparison group.

However, interpretations of these studies are not straightforward, since people on calorie restriction also change their food choices. In the mentioned study, calorie restricted subjects strictly avoided processed foods, such as refined carbohydrates, desserts, snacks, and soft drinks [30]. Furthermore, one prospective observational study in the general Swedish population found that moderately high caloric intake was associated with lower total mortality in women, and a similar trend in men [31]. In addition, most observational studies do not support the idea that weight loss is beneficial. It is therefore premature to state that eating less without altering food choices is healthy.

In spite of these controversies, calorie restriction is widely believed to promote health for the average Westerner, and a common conception is that they do so independently of which foods are consumed. Energy intakes in excess of expenditures are often thought to be the sole explanation of the high rates of overweight in Western populations. One of the laws of thermodynamics is then often cited, the one saying that energy is constant and cannot disappear. However, other laws of thermodynamics, stating that energy can take various forms, including heat, and that conversion from one form of energy to another is more or less efficient, are rarely considered [32]. Metabolic utilization of energy from foods can be more or less efficient, depending on whether it is stored in the form of protein, fat or carbohydrate [32]. Highly relevant in this context is the finding in animal experiments of decreased body temperature on a low-calorie diet [33].

The emerging notion that calorie restriction is not independent of food composition finds additional support from recent findings in the fruit fly Drosophila, one of the most extensively studied species in this context [34]. In these experiments, reduction of either dietary yeast or sugar reduced mortality and extended life span, but to an extent that was unrelated to the calorie content of the food, and with yeast having a much greater effect per calorie than sugar. Recent experiments with caloric restriction in rats suggest that protein intake should be maintained at reasonably high levels in order to improve mitochondrial cell function and prevent loss of muscle mass (sarcopenia) [35].

To summarize, calorie restriction, in accordance with the guidelines of The Calorie Restriction (CR) Society (calorierestriction.org), has several apparent benefits, but only counting calories may sometimes be misleading. Reduction of waist circumference and fat mass is preferable to crude weight loss. If overweight persons restrict their food intake they should be advised to concomitantly change their consumption patterns. Substituting fruit, vegetables, root vegetables and lean meat for bread, pasta and other Western staple foods generally leads to decreased energy intake despite increased or unaltered amounts of food.

Mediterranean-style diets

International comparison from the second half of the 20th century found lower rates of ischemic heart disease in Mediterranean countries like Greece, Italy, Spain and former Yugoslavia, most notably before the age of 65. In the Seven Countries Study, Crete had the lowest incidence of ischemic heart disease at follow-up after 10 years [5] and after 20 years [36]. After 25 years, total mortality was lowest in the Cretan men, although ischemic heart disease mortality now had slightly surpassed the two Japanese groups [37]. For these reason, the Cretan diet has become a standard model for Mediterranean-style diets [38]. In 1948, 12 years before the beginning of the Seven Countries Study, the major sources of energy in the Cretan diet were cereals (mainly sourdough bread), nuts, pulses, olives, olive oil, vegetables and fruit, together with limited quantities of goat meat and milk, game, and fish [39]. Wine was consumed regularly. The intake of ß-casein A1, a protein in milk which has been proposed to cause atherosclerotic disease, was particularly low, less than 0.5 g/day [40].

The Lyon Diet Heart Study found reduced mortality and morbidity (non-fatal disease) of ischemic heart disease after advice to follow a Mediterranean-style diet [24]. However, the Mediterranean group was given more intense lifestyle education than the control group, who received ”usual care", posing a possible bias to the study. In addition, the Mediterranean group was provided with a margarine based on rapeseed-oil, enriched with alpha-linolenic acid (plant-based omega-3 fat).

Today, diabetes type 2, and possibly ischemic heart disease, are apparently common in Crete [41]. Hypertension and stroke have been prevalent a long time in Mediterranean populations, including the Cretans [42, 43].

In conclusion, Mediterranean diets are apparently a step in the right direction for many people, but they may not be the best choice for long-term human health.

Omega-3 enriched diets

One of the strongest beliefs held about healthy food is that fatty fish prevents heart disease, and that omega-3 polyunsaturated fatty acids are the main reason [44, 45]. However, the evidence is not by far as solid as it may seem. In 2004, a Cochrane meta-analysis of randomized controlled trials found no net benefit on cardiovascular disease, total mortality, or cancer [46]. A shorter report of this meta-analysis was later published in the British Medical Journal [47]. Criticism of these findings has largely focused on the fact that exclusion of one trial, DART-2 [25], seems to change the results in favor of omega-3 [48, 49]. However, DART-2 is not the only trial showing negative effects of omega-3 fat in patients with ischemic heart disease [50]. Furthermore, the results of the Cochrane review suggest the presence of publication bias, such that large trials do not show a positive effect [46]. Much of the criticism of the short report <http://www.bmj.com/cgi/content/abstract/332/7544/752>is taken into account in the long one [46]. The debate will most certainly continue.

Even the statement that cardiovascular disease was uncommon in the Greenland Inuit and related populations, as long as they pursued their traditional lifestyle, has recently been questioned [51]. In a review of 20th century clinical and autopsy studies, and mortality statistics, from Greenland, Canada and Alaska, atherosclerosis and cardiovascular disease was not lower among the Inuit than among white comparison populations.

Sodium restriction

A starting point for discussions about salt and health was a French experiment 100 years ago showing raised blood pressure after high salt intake roughly [52]. Considerable evidence now suggests that restriction of dietary sodium below 100 mmol Na/day (<6 g sodium chloride or <2.4 g sodium per day) will reduce blood pressure and prevent cardiovascular disease in people with hypertension [53]. Since only a minority of middle-aged and elderly Westerners have optimal blood pressure (<120/<80 mm Hg), and since low levels are more healthy than average or high levels, most people would seem to benefit from a low salt intake. Several studies suggests that dietary salt is a contributing factor in the development of stroke and heart failure, particularly among overweight people, and possibly independently of blood pressure (See sections 4.2 and 4.9). A correlation between sodium intake and stroke has also been noted among Europeans [54], as well as in China and Japan [55]. The influence of dietary salt on ischemic heart disease is more controversial, but here, again, the risks with high salt intake may highest for overweight subjects.

Vitamins and minerals

Ever since the discovery of man’s dependence on vitamins and minerals, and the abundance of such substances in fruit and vegetables, there has been much interest in their role for human health. Deficient intakes of many vitamins and minerals, including a number of trace elements, have been suggested as underlying causes of Western disease, as will be noted in the following chapters. Much of the evidence comes from epidemiological studies. However, when these nutrients later have been given in large-scale randomized double-blind controlled trials, essentially no beneficial effects have been seen [56]. A recent Cochrane meta-analysis found that supplementation with vitamin A and vitamin E may actually increase mortality, while the impact of vitamin C and selenium needs further study [57].

Low glycemic index (GI) foods and carbohydrate restriction

In the year 1825, Brillat-Savarin, the influential French writer on food, cooking and nutrition, suggested that high-starch foods were a major cause of corpulence in his book ”The Physiology of Taste” (http://www.gutenberg.org/etext/5434). His authority reached a few of the medical practitioners in France and England, and, in 1862 in London, the now famous William Banting was advised by his physician to ”...abstain as much as possible from bread, butter, milk, sugar, beer, and potatoes...”, and lost 21 kg in the following 12 months. By tradition, this often cited diet has been described as a low-carbohydrate diet rather than one based on meat, fish, fruit and vegetables, which it was. The proceeding history of carbohydrate restriction includes proponents such as Stefansson in the 1920s, Pennington, Cleave and Mackarness in the 1950s, Donaldson and Lutz in the 1960s, Atkins in the 1970s (and again in the 1990s), and more recently dietary programs such as the Zone, the Carbohydrate Addict’s Diet, Protein Power, South Beach Diet, Sugar Busters and many others.

A low GI food is one that, despite being rich in carbohydrates, does not increase blood sugar as much as another food with the same amount of carbohydrate. Carbohydrate restriction refers to reduction of the amount of carbohydrate in the food without necessarily changing the GI. If you multiply the GI by the absolute amount of carbohydrate you get the glycemic load [58]. The rationale behind low GI and restriction of carbohydrates is to reduce the rise in blood sugar and insulin secretion after a meal, which in turn is intended to prevent insulin resistance, overweight, glucose intolerance, type 2 diabetes, dyslipidemia and the metabolic syndrome [59].

However, an independent beneficial effect, irrespective of food source, on these variables is not unequivocally supported by available evidence [60-67]. In people with diabetes, avoiding excess increases in blood sugar after meals is undeniably beneficial, but exchanging carbohydrate for fat may pose other long-term threats. In overweight or obese subjects, initial weight loss in the first few months is usually more pronounced on a very, very low-carbohydrate diet such as the Atkins diet, but energy intake and adherence seem to be more important than choice of dietary program for long-term (>1 year) weight maintenance [61, 62]. Generally, serum triglycerides are reduced, while low density lipoprotein (LDL) cholesterol is slightly increased [66]. Although triglycerides usually decrease more than LDL increases, the net health benefit of this is uncertain [68]. Exclusively changing the GI seems to have little impact on body weight [69] and cardiovascular risk factor levels [70].

A large, randomized, high-quality trial compared four weight-loss diets with varying carbohydrate content in women with average BMI 32 (range 27-40), i.e. the Atkins (very-low carbohydrate), Zone (moderate carbohydrate), LEARN (traditional high carbohydrate), and Ornish (very-high carbohydrate) diets [71]. Weight loss, the primary outcome, was modest in all groups: after one year, weight loss in the Atkins group was 4.7 kg (95% confidence interval 6.3-3.1 kg), compared to 1.6 kg (2.8-0.4 kg) in the Zone, 2.6 kg (3.8-1.3 kg) in LEARN, and 2.2 kg (3.6-0.8 kg) in the Ornish group. There was no statistically signifcant difference in weight loss between the Atkins and LEARN programs at 12 months. However, secondary outcome variables were comparable or more favorable in the Atkins group. For example, systolic blood pressure was reduced by 7.6 (±11.0) mm Hg in the Atkins group, compared to 3.1 (±9.3) mm Hg in the LEARN group (p<0.05). No effect was found on fasting insulin or glucose. This study does not suggest that a traditional high-carbohydrate diet program is more beneficial than the Atkins diet.

However, the long primate history of fruit eating [72], the high activity of human salivary amylase for efficient starch digestion [73] and some other features of human mouth physiology [74], as well as the absence of Western disease among starch-eating traditional populations [75, 76], including the Kitavans that we studied, suggest that humans are well prepared for a high carbohydrate intake from non-grain food sources. Although restriction of all types of carbohydrates may provide some benefit for subjects with diabetes type 2, it seems unlikely that dietary carbohydrate is a primary cause of Western disease.

Red wine

The claimed benefits of red wine are so often reported that they may seem to be a proven fact, and the critical voices do not get much attention. As always, we have a possible bias in the form of confounders. Furthermore, in order to get a true protection against cardiovascular disease you may need to drink so much every week that your brain and liver are damaged [77]. In epidemiological studies, the difference in mortality between people who drink 2 glasses of wine per day and those who drink once a month is negligible or non-existent. Enthusiastic reports about resveratrol, a substance in red wine which prolongs life in mice that are fed high-fat/sucrose diets, often forget to mention that the doses used correspond to more than 700 bottles of wine per day [78].

Other concepts

There is a large number of additional philosophies about diet and health, many of which will be commented upon in my later writing. The idea that Soy foods are healthy is largely based on the Vegetarian tradition, and both have had considerable impact on nutritional science despite inconsistent research findings. Red meat is basically an epidemiological story without strong evidence from other research areas. The Antioxidant story mainly emerged from intriguing hypotheses in molecular biology, but randomized double-blind controlled trials with antioxidants have essentially failed to show any benefit [56].

Conclusions

Foods that are generally perceived as healthy, most notably fruit and vegetables, are apparently a better choice than foods that are not perceived as healthy. Nevertheless, many of the prevailing concepts are not firmly based on good evidence. Nutritional recommendations for public health are resting on such unstable ground that evolutionary medicine may provide an important complement to traditional scientific methods [79, 80]. Reading the scientific literature through the lens of evolutionary biology can make it easier to understand the extremely complex relationships between diet and health.

Dietary advice to prevent and treat common western diseases should be designed in accordance with human's biological heritage as much as possible. Foods that have been part of the human staple diet for less than 10,000 years should be critically examined before they are recommended as staple food. Even the risks with foods that were available during the Paleolithic era (Old Stone Age, approximately 2.5 million - 10,000 years ago), but which may contain anti-nutritional substances, should be carefully examined, in particular foods that are consumed in large quantities on a daily basis.

1. Kritchevsky, D. History of recommendations to the public about dietary fat. J Nutr, 1998; 128: 449S-452S